M.C. White, Chem 153
Hydrozirconation -292-
Week of November 18, 2002
Alkene/Alkyne Hydrozirconation
ZrI V
C6H13
Olefin binds weakly to vacant d
orbital on Zr via σ-donation
(π-backbonding is not possible
because the complex has no d
electrons).
Cl
H
R
Schwartz's reagent, 16e - (d0)
(stoichiometric)
benzene, rt, N2
Schwartz JACS 1974 (96) 8115.
Morokuma OM 1993 (12) 2777.
ZrI V
benzene, rt, N2
16e - (d0)
Moisture and O2 sensitive alkylzirconium
product. Olefin insertion into the Zr-C bond
has never been observed.
ZrI V
H
Cl
R
18e - (d0)
Cl
H
1 eq
ZrI V
H
Internally metalated alkylzirconium
complexes rapidly isomerize at rt via
β-hydride elimination, reinsertion
sequences to the least sterically
hindered 1o alkylzirconium product.
ZrIV
Cl
Zr(Cl)Cp 2
Zr(Cl)Cp 2 H
+
Cl
H
catalytic
Cp2(Cl)Zr
H
benzene, rt, N2
H
Zr(Cl)Cp 2
84:16
Stereospecific cis hydrometalation occurs with high
regioselectivity in formation of the least sterically hindered
vinylzirconium species. The use of excess Schwartz's reagent
results in higher regioselectivities via formation of a dimetalated
alkyl intermediate that preferentially β-hydride eliminates at the
more sterically hindered Zr center.
Schwartz JACS 1975 (97) 679.
H
Zr(Cl)Cp 2 H
Zr(Cl)Cp 2
+
98:2
M.C. White, Chem 153
Hydrozirconation -293-
Week of November 18, 2002
Functionalization
Electrophilic functionalization
HCl (dilute)
R
>99% octane
H
ZrIV
Cl
Br2
ZrIV
Br
96%
R
(note :NBS and
O NCS also work)
16e - (d0 )
Cl
R
R
Br
ZrI V
+
Br
Cl
Br
O
16e - (d0 )
Cl
alkylzirconium and alkenylzirconium
compounds react readily with a range
of electrophiles.
80%
H2O2, NaOH
69%
Reaction of Br2 with chiral alkylzirconium complexes
affords alkyl bromides with retention of configuration
at the stereogenic carbon center. Likewise,
alkenylzirconium complexes react with Br2 to give
vinyl bromides with retention of olefin geometry.
Because the alkylzirconium complex is formally d0,
product formation via an oxidative addition/ reductive
elimination
sequence
is
not
reasonable.
Functionalization is thought to proceed via a σ-bond
metathesis mechanism.
CO insertion/ Zr acyl functionalization
R
R
HO
Schwartz ACIEE 1976 (15) 333.
O
HCl (dilute)
H
R
>99% n-heptanal
R
51% methyl
n-heptanoate
O
Br2, MeOH
ZrI V
Cl
ZrI V
CO (1.5 atm), rt
R
16e - (d0 )
O
Cl
R R'
insertion proceeds
with retention of
configuration at C.
O
MeO
OH
H
R
R'
BF3 · OEt2
16e - (d0 )
O
-HC=CH-, R = C 4H9, R'= Ph , 69%
-CH2CH2 -, R = (CH2 )2 OBn, R'= Ph, 74%
O
H2O2, NaOH
Schwartz JACS 1975 (97) 228.
Hanzawz ACIEE 1998 (37) 1696.
HO
n-heptanoic acid, 77%
R
Transmetallation of alkenylzirconocenes
ZrIV
Cl
R
16e - (d0 )
LnM-X
transmetalation
M = Al, B, Cu, Hg,
Ni, Pd, Sn, Zn
Ln M
+
R
ZrIV
Cl
X
Wipf Tetrahedron 1996 (52) 12853.
M.C. White, Chem 153
Hydrozirconation -294-
Week of November 18, 2002
Synthetic applications
Hydrozirconation/transmetalation sequence in the total synthesis of Fostriecin. Jacobsen ACIEE 2001 (40) 3667.
O
Me
1. [Cp 2Zr(H)Cl], CH2Cl 2
2. Me2 Zn (-78o C), 10 min
i-PrO
O
3.
R
R
Me2Zn
O
O
Zr(Cl)Cp 2
O
Me
R
ZnMe
i-PrO
O
H
OH
~ 45%
O
ZrIV Cl
Me
Hydrozirconation/bromination sequence in the total synthesis of FK 506. Schreiber JACS 1990 (112) 5583.
TIPSO
MeO
1. [Cp2Zr(H)Cl](3 eq),
benzene, 30-40 oC
2. NBS, rt, 25 min
R
TIPSO
TIPSO
Me
Me
MeO
MeO
Zr(Cl)Cp 2
Br
86%
Me
Hydrozirconation/Negishi coupling sequence in the total synthesis of FR901464. Jacobsen JACS 2000 (122) 10482.
H
O
I 1. [Cp2Zr(H)Cl],
THF, 0oC
Cp2(Cl)Zr
I
O
I
2. ZnCl 2, THF, 0oC
3. Pd(PPh3)4 (6.5mol%)
TESO
N3
TESO
TESO
O
O
O
O
O
O
I
80%
N3
obtained via hydrozirconation/
iodination sequence
M.C. White, Chem 153
Hydrozirconation -295-
Week of November 18, 2002
Hydridic character of Schwartz’s reagent
O
R
ZrI V
δ+
OH
H
H3O+
O
R
OZr(Cl)Cp2
Cl
R
H
δ-
H
H
OH
R'
The hydridic character of the highly ionic Zr-H bond
is demonstrated in its ability to reduce a variety of
carbonyl functionalities to Zr alkoxides at a rate
competative with olefin hydrozirconation.
H3O+
R
O
R'
R
R'
H
H
OH
R
OR'
H3O+
R
H
H
Schwartz ACIEE 1976 (15) 333.
Reduction of 3o amides directly to aldehydes.
Direct reduction of Evan's N-acyl oxaolidinone (generally a 2 step procedure
involving transamination to the Weinreb amide followed by LAH reduction to the
aldehyde).
O
O
O
ZrIV
O
Cl
O
H
(1.5-2 eq)
R
NEt3
R
THF, rt, 20-30 min
R = p-CNC6H4-, 90%
p-NO2C6H4-, 81%
p-OMeC 6H 4-, 99%
H
MeOC(O)C8H16-, 74%
N
MeO
O
H3C
H
Cp2Zr(H)Cl (1.5-2.0 eq)
THF, rt, 20-30 min
MeO
Ph
92%
Why don't the product aldehydes become reduced in situ? According to the proposed mechanism, the aldehyde is masked as iminium ion intermediate which decomposes upon
aqueous workup to release the aldehyde product.
O
R
OZr(H)Cp2
N
R''
R' Cp 2Zr(H)Cl
R
N
R''
Cl
H
OZrCp 2
R'
H
Cl
R'
R
R'
N
R''
R
Cp2Zr(O)
H
Cl
N
H2O
R
O
R''
Georg JACS 2000 (122) 11995.
M.C. White, Chem 153
Alkene/C-M insertions -296-
Week of November 18, 2002
Dimerization, Oligomerization, Polymerization
n R
LnM n
oligomer, n= 3-100
polymer, n > 100
R
R = CH3, H
termination via
β -hydride elimination
L nM n R
R
dimer
R
H
R
R
n
L nM n
LnM n
termination via
β -hydride elimination
H
L nM n
propagation
via insertion
note that there is no
oxidation state change
to the metal throughout
the cycle
R
R
LnM n
H
L nM n
R
L nM n
R'
R'
LnM n
K1
H
+
R'
K1 has been found to depend on the
number and size of alkyl
substituents on the olefin. Increased
substitution and steric bulk of the
olefin leads to decreased rates of
binding to the metal complex.
LnM n H
K2
β -hydride
elimination
LnM
n
H
‡
β -hydride
addition
H
R'
L nM
It has been observed that with early, high-valent metals
(e.g. Zr(IV), d0) the equilibrium lies to the left (K2 >
1)whereas with late, low-valent metals (e.g. Pd(II), d8)
the equilibrium lies to the right (K2 < 1). Electron density
at the metal is thought to favor the hydrido-alkene
species via stabilizing π-backbonding into the olefin π*.
n
Hoffmann JACS 1976 (98) 1729.
Labinger ACIEE 1976 (15) 333.
M.C. White, Chem 153
EM Polymerization -297-
Week of November 18, 2002
Ziegler Natta Polymerization
"What has guided my research has been solely the wish to do something that gave me joy,
that is a joy from finding, somehow or somewhere, something really novel...At least at the
outset, the only thing of value aimed for is an accretion in knowledge, rather than new
applications." Karl Ziegler.
In an attempted distillation of ethyllithium, Ziegler
observed ethylene and higher α-olefins. He reasoned
that the following process was occuring:
Li
∆
+ LiH
β -hydride
elimination
propagation
Li
∆
+ LiH
β -hydride
elimination
Organoaluminum compounds such as Et2AlH displayed even higher activities
towards ethylene resulting in higher aluminum alkyls that could be readily
hydrolyzed to produce higher alcohols.
Al
H
100oC
Al
Al
Ziegler found that traces of Ni salts (accidently
incorporated during cleaning the reactor) resulted only in
butene and R2AlH.
Al
Ni salts
Al
H
+
Eisch J. Chem. Edu. 1983 (60) 1009.
If traces of Ni salts could make such a dramatic impact on the
course of ethylene oligermerizations, Ziegler wondered what other
metals may do... An exploration of this curiosity led to the
TiCl3/Et2AlCl catalyzed Zeigler Natta polymerization (Nobel Prize,
1963) which is currently used commercially to produce ~ 15
million tons of polyethylene and polypropylene annually.
The stereochemistry of polypropylene significantly influences its physical properties. Isotactic
polymers are the most useful commercially with such physical properties as high tensile
strength and high melting points (~165oC).
Ziegler's original process for ethylene polymerization:
TiCl4/AlR 3
n
polyethylene
Ziegler Angew. Chem. 1955 (67) 541.
Natta extends this to propylene polymerization. He finds that by
using crystalline TiCl3, the regularity of the surface of the
heterogeneous catalyst is increased. This results in a greater
stereospecificity in polymerization with the amount of desired
isotactic polypropylene inreasing from 40% to 90%.
syndiotactic: long sequences having
the opposite stereochemistry at
adjacent carbons. Physical properties:
semicrystalline with a melting
temperature ~ 100oC.
atactic: stereorandom polymer that behaves as an amorphous
gum elastomer.
polypropylene
TiCl3/AlR 3
n
Natta Angew. Chem. 1956 (68) 393.
isotactic: stereoregular material, long
sequences
having
the
same
stereochemistry at adjacent carbons.
Physical
properties:
crystalline
thermoplastic.
For other polymer tacticities see: Coates Chem. Rev. 2000 (100) 1223.
M.C. White, Chem 153
EM Polymerization -298-
Week of November 18, 2002
Cossee mechanism for Ziegler Natta polymerizations
Cossee mechanism for Ziegler Natta heterogeneous polymerization.
According to the Cossee mechanism, propagation of the polymer occurs exclusively at the Ti center. The role of the alkyl aluminum
species is thought to be that of initiator by alkylating the TiCl3.
Cl
Ti
Cl
Ti
Cl
Cl
Cl
Cl
Ti
Ti
olefin
coordination
Cl
Cl
Cl
Ti
Cl
Ti
Cl
Cl
Ti
Cl
Cl
Ti
Cl
Cl
Cl
Representation of a
TiCl3 lattice with an
open coordination site
on the surface
Ti
Ti
Cl
cis-carbometalation via a
concerted 4-membered TS.
Cossee TL 1960 (17) 12.
Cossee stereochemical model for isotactic polypropylene formation:
Cl
Ti
Cl
Ti
si-face
favored
Cl
Cl
Polymer
Ti
Cl
Cl
Ti
Cl
re-face
disfavored
Ti
Cl
Ti
Polymer
Cl
Cl
Ti
Representation of a stereogenic Ti center on the edge of a chiral TiCl3
crystal. The growing polymer occupies the open quadrant. The olefin
preferentially binds via its si-face placing its methyl substituent trans to
the bulky polymer chain. Modern MgCl2-supported Ziegler Natta
catalysts are highly stereoselective resulting in formation of essentially
Cossee TL 1960 (17) 17.
Brintzinger ACIEE 1995 (34) 1143. only the isotactic polymer.
Cl
Cl
Ti
M.C. White, Chem 153
EM Polymerization -299-
Week of November 18, 2002
Metallocenes as homogeneous polymerization catalysts
No reaction is observed in the absence of Et2AlCl or Et3Al. Both Et2AlCl and Et3Al alone produce only
oligomers. Unlike the heterogeneous Ziegler-Natta polymerization catalysts, these catalysts are ineffective
at polymerizing α-olefins (propylene).
Cl
TiI V
Cl
n
Et2AlCl
polyethylene
Natta JACS 1957 (79) 2975.
Breslow JACS 1957 (79) 5072.
Breslow's proposed mechanism:
Cl
Cl
Al
δ+
TiIV
Cl
Et2AlCl
Cl
Al
δ-
Cl
Cl
Cl
Cl
Al
δ-
Cl
TiI V
TiIV
cis- migratory
insertion
Cl σ-bond metathesis?
Cl
TiI V
δ+
Polarization of the Ti-Cl bond by the
Lewis acidic Al center promotes
ethylene coordination/insertion.
propagation
Cl
Cl
Al
Cl
TiI V
δ+
Cl
Al
Cl
Cl
H
P
P
Breslow JACS 1959 (81) 81.
β -hydride
elimination
TiIV
H
Cl
(termination)
Al
H
Cl
Cl
TiI V
P
M.C. White, Chem 153
EM Polymerization -300-
Week of November 18, 2002
Activation by MAO
Water is generally considered a poison for early transition metal
polymerization catalysts. Trace amounts of water were reported to cause a
significant increase in the rates of ethylene polymerization by
Cp 2TiEtCl/AlEtCl 2 system. It was later found that water activated
analogous Zr complexes which were typically unreactive towards even
ethylene polymerizations to highly active catalysts for both ethylene and
propylene polymerization.
Activation by MAO:
Dimethylzirconium complex
It is postulated that the highly Lewis acidic Al centers in MAO "abstract" CH3_ resulting
in a cationic Zr complex and a weakly coordinating (CH 3-MAO)- counterion that may or
may not be weakly associated with the metal.
δ-
H 3C
IV
Zr
ZrI V
MAO
Me
δ+
ZrI V
Me
R'
Al(MAO)
Me
R'
R' = Me or Cl
No polymerization activity
R3Al
or
H 3C
Al(MAO)
+ H 2O
ZrI V δ+
ZrI V
Me
atactic polypropylene
n
or
δ-
n
H 3C
In situ formation of MAO (methylalumino oxane). Hydrolysis of
AlMe3 by water results in the formation of a mixture of oligomeric
aluminoxanes (exact compositions and structures are still not known).
Preformed MAO is equally effective as an activator of Cp2ZrMe2 and
Cp 2ZrCl2 catalysts towards olefin polymerizations.
polypropylene
Dichlorozirconium complex
Me
O Al
Me
nAlMe3
Me
Al
O
Al
O
Al
nH2O
O
n
Al
O
Me
MAO (methlylalumino oxane)
Barron JACS 1995 (117) 6465.
Al(MAO)
ZrI V
Cl
Cl
Me
MAO
ligand exchange (via
σ-bond metathesis?)
ZrI V
Me
MAO
as above
Me
n
Kaminsky ACIEE 1976 (15) 630.
Kaminsky ACIEE 1980 (19) 390.
Brintzinger ACIEE 1995 (34) 1143.
M.C. White, Chem 153
EM Polymerization -301-
Cationic metallocene catalysts
First preformed and spectroscopically characterized cationic complex capable of ethylene
polymerization. This work supports the proposal that cationic Zr and Ti complexes formed upon olefin
binding are the active polymerization catalysts.The low polymerization activity was attributed to the
coordinated THF which competes with ethylene for binding.
BPh4
ZrI V
CH3
CH3
AgBPh 4 (1 eq)
ZrIV
THF
O
CH3
Jordan JACS 1986 (108) 7410.
First well-characterized cationic zirconocene catalyst capable of propylene polymerization at high rates.
H 3C
ZrIV
CH3
CH3
Marks JACS 1991 (113) 3623.
B(C6F5)3 (1 eq)
C6H6
ZrI V
CH3
B(C6F5)3
Week of November 18, 2002
M.C. White Chem 153
EM Polymerization -302-
Week of November 18, 2002
Chiral metallocene catalysts
Brintzinger's C2-symmetric catalysts/ enantiomorphic site control
1-Naphthyl
polymer chain-end control: the stereochemistry of
the newest stereogenic center on the growing
polymer controls the stereochemistry of monomer
addition.
enantiomorphic site control: chiral ligand
overrides the influence of the polymer chain end
and controls the stereochemistry of monomer
addition.
Me
Cl
Zr
Cl
Cl
Zr
Me2Si
Cl
Me
Cl
Zr
Cl
1-Naphthyl
(±) ethylenebis(indenyl)
zirconium dichloride
(±) ethylenebis(tetrahydroindenyl)
zirconium dichloride
MAO
MAO
MAO
50oC
60o C
50oC
Ln M
91% isotacticity,
7700 activity (kg pol/molZr·h),
Mw = 12,000.
Brintzinger ACIEE 1985 (6) 507.
>99% isotacticity,
875 activity (kg pol/molZr·h),
Mw = 920,000.
Paulus OM 1994 (13) 954.
Ln M
78% isotacticity,
188 activity (kg pol/molZr·h),
Mw =24,000.
Paulus OM 1994 (13) 954.
polymer chain-end control:
stereoerror is propagated.
P
enantiomorphic site control:
stereoerror is corrected by the
catalyst.
P
Proposed model for isospecific polymerization
polymer chain is
in open quadrant
‡
H P
P
Zr
Zr
Zr
P
H
H
olefin binds such that its
α-substituent is trans to the
bulky substituent on the growing
polymer chain
Cl
Zr
Cl
H
stabilizing α-agostic interaction in the
TS is thought to rigidify the TS for olefin
insertion
thereby
increasing
the
stereospecificity of insertion.
meso ligands give atactic
polymers.
Grubbs Acc. Chem. Res. 1996 (29) 85.
Coates Chem. Rev. 2000 (100) 1223.
Ewan JACS 1984 (106) 6355.
M.C. White, Chem 153
EM Polymerization -303-
Week of November 18, 2002
Torsional isomers in stereoselective propylene polymerization
R* =
R*
Cl
Zr
neoisomenthyl
Cl
this catalyst led to the formation of
highly isotactic, high molecular
weight polypropylene, with purely
enantiomorphic site control at low
temperature.
*R
Me
R* =
MAO
in contrast, polymerizations with
the
neomenthyl-substituted
metallocene catalyst were "much
less selective"
neomenthyl
Erker JACS 1993 (115) 4590.
R*
R*
R
13C NMR
and 1H NMR studies at -50 oC showed that
in solution the neoisomenthyl-substituted metallocenes
exist primarily as a single, C2-symmetric species. In
contrast, the neomenthyl-substituted catalysts exist as a
4:1 ratio of C 2:C 1-symmetric metallocene species. The
Zr
R
Zr
R*
R* =
C1-symmetric
C2-symmetric
neomenthyl
authors speculate that with the neomenthyl-substituted
catalysts the switching between C 2 and C1-symmetric
metallocene species may have given rise to the
formation of alternating isotactic and nearly atactic
R*
Me
Me
sequences along the growing polymer chain.
Isotactic
Atactic
M.C. White, Chem 153
EM Polymerization -304-
Week of November 18, 2002
Torsional isomers in stereoselective propylene polymerization
Recall:
Isotactic polymer
Often up to 100 % isotactic pentad
(fraction of stereosequences
containing 5 adjacent isotactic
centers)
Zr
Zr
P
chiral- racemic
Atactic polymer
6.25 % isotactic pentad
(fraction of stereosequences
containing 5 adjacent
isotactic centers)
P
achiral-meso
ki
The bridge between the indenyl ligands
is removed to allow rotation about the
metal ligand bond axis. Bulky phenyl
substituents are incorporated into the
indene ligand to inhibit the rate of
ligand rotation such that it is slower
than monomer insertion but faster than
propagation/termination. The result is
production of an isotactic-atactic
stereoblock copolymer.
note: another way in which
polymer tacticity is often
described is by the
stereochemical relationship
between
adjacent
stereogenic centers: "m" for
meso and "r" for racemic.
For example, an isotactic
pentad would be [mmmm]
Zr
P
Observation
of
both
the
racemic-like
and
meso-like
compounds in the crystal unit cell
indicates that the torsional isomers
are energetically similar.
Achiral meso-like
Chiral racemic-like
k pi
Zr
k -i
P
k pa
Me
Me
Block copolymer is produced with alternating isotactic-atactic domains
Isotactic pentad
Atactic block
Isotactic pentad content = 6.3-28.1 %
Isotactic pentad
Waymouth Science 1995 267 217-219.
M.C. White/ Chem 153
Oligomerization -305-
Week of November 18, 2002
SHOP (Shell Higher Olefin Process)
P
NiII
Ph
late metal is highly
tolerant of oxygenated
functionality
PPh3
O
SHOP process is operated on a 1 million ton
capacity and constitutes one of the largest
applications of homogeneous catalysis by a
transition metal.
activity = 6000 mol ethylene/mol Ni
(40 atm)
Proposed mechanism:
n
99% linear
98% α-olefins
up to C 30
50 oC, toluene
(can be run in acetone or EtOH)
Catalyst activation:
Ph2
P
Ph
NiII
PPh3
O
Ph
Ph2
Ph
P
NiII
PPh3
Ph2
P
NiII
O
Ph
Keim and Kruger ACIEE 1978 (17) 466.
Keim ACIEE 1990 (29) 235.
Ph
O
Ph
Ph2
Ph 2
P
P
NiII
H
Ph
Ph 2
P
NiII
Ph
O
Ph 2
P
NiII
n
branching pathway
n
Ph
n associative
displacement
Ph
Ph2
P
H
NiII
O
H
O
hydride migratory insertion/
ethylene association
Ph 2
P
H
NiII
O
Ph2
P
NiII
Ph
n
Ph2
P
NiII
termination via
β -hydride elimination
Ph
O
O
Ph
Formation of the bis ligand
complex results in irreversible
catalyst inactivation.
Ittel J. Mol. Catal. 1987 (41) 123.
etc..
O
Ph2
P
NiII
Ph
If there is β-hydride elimination, why don't we see
significant branching? Possibilities include 1.
associative displacement of the α-olefin oligomer is
rapid relative to cis hydrometallation to the branched
alkyl 2. branched alkyl insertion into ethylene is
unfavorable.
Ph
O
H
n
O
alkyl migratory insertion/
ethylene assocation, repeat..
(propagation)
M.C. White, Chem 153
LM Polymerization -306-
Week of November 18, 2002
Brookhart’s cationic Ni(II) polymerization catalyst
The rate of associative displacement of
the olefin (leading to chain termination
and oligomeric products as in the SHOP
process) is retarded in these systems by
the steric bulk of the ligand which
blocks the axial positions above and
below the plane of the Ni complex (see
Mechanism, pg 46,47).
Br
N
NiII
Br
N
MAO
branched polyethylene (PE)
toluene, 25oC
(1 atm)
Mw = 410,000
activity = 1.53 x 105 TO/h· mol Ni, 1.8 g PE
Brookhart JACS 1995 (117) 6414.
Excellent review: Brookhart Chem. Rev. 2000 (100) 1169.
Proposed catalytic cycle:
71 methyls (branches)/1000 C
catalyst activation
N
Br
Ni
N
MAO
II
N
Br
see EM Polymerization,
pg 300
CH3Al(MAO)
CH3
NiII
N
N
etc...
N
N
insertion
N
n
II
Ni
H
branching
propagation
H
N
Ni
N
CH3Al(MAO)
CH3
NiII
propagation
Linear high Mw
polymers
n
m
II
NiII
N
N
β-hydride
elimination
n
N
NiII
H
N
N
re-insertion
w/opposite
regioselectivity
etc...
H
N
NiII
NiII
n
N
propagation
N
m
n
termination
n
N
NiII
N
N
associative
displacement
H
N
NiII
N
Low Mw polymers
H
NiII
H
N
m
Low Mw polymers
n
Branched
high Mw
polymers
M.C. White, Chem 153
LM Polymerization -307-
Week of November 18, 2002
Grubbs’neutral Ni(II) polymerization catalyst
Unlike heterogeneous Ziegler Natta and homogeneous cationic metallocene
polymerization catalysts (poisoned by O,N, and S heteroatom functionality),
neutral Ni(II) catalyst 1 is highly tolerant of oxygenated functionality. Ethlene
polymerizations with 1 can be run in the presence of up to 1500 eq. of ether,
ketone, and ester additives without significantly inhibiting catalyst activity.
O
Ph
II
Ni
i-Pr PPh3
N
1, cat
+
i-Pr
1
cat.
n
toluene, 10oC external bath
(~7 atm)
10oC
(~7 atm)
Mw > 250,000
activity = 3.7x 10 6 g PE/mol Ni/hr
>10 branches/1000 C's
N
Ph
Ni
O
NiII
H
O
PPh3
styrene, PR3
(as in SHOP)
H
n
NiII
PR3
PR3
O
observed by 31P NMR
The rate of associative displacement of the olefin (leading to
chain termination and oligomeric products) may be retarded
in these systems (as in the Brookhart system) by the steric
bulk of the ligand which blocks the axial positions above and
below the plane of the Ni complex. The resting state of the
catalyst appears to be the phosphine complex (observed by
NMR at various stages throughout the cycle). Neutral Ni(II)
complexes are less prone to β-hydride elimination that
cationic Ni(II). This may account for the more linear PE
observed in these systems vs. the cationic Brookhart systems.
N
II
m
OH
incorporation of polar
monomer: 22 Wgt %
Branch/1000 C = 9
Mw = 73, 800
Proposed catalytic cycle:
N
n
OH
(225 eq.)
linear polyethylene (PE)
Unlike the Brookhart cationic Ni(II)
polymerization catalysts, catalyst 1
produces highly linear PE.
toluene,
external bath
N
NiII
N
H
O
N
H
Ni
NiII
O
O
n
II
PR3
N
NiII
O
PR3
observed by 31P NMR
H
N
N
NiII
O
n propagation
NiII
O
Grubbs Science 2000 (287) 460.
M.C. White, Chem 153
LM Polymerization -308-
Week of November 18, 2002
Ligand mediated activation
Neutral Ni (II) complex is activated via formation of a borane carbonyl adduct on the ligand towards oligomerization and polymerization of ethylene. Upon formation of
a hypervalent boron"ate" complex which places a positive charge on the coordinated carbonyl oxygen, induction via the ligand's π-system is translated into a loss of
electron density at the Ni center. At one extreme, resonance structure B may be draw with a full positive charge at the Ni center. As seen in the Brookhart and Grubbs
systems, ligand steric bulk in the axial positions is required to effect high Mw polymerization rather than SHOP type oligermerization with Ni.
N
CH2Ph
Ni
O
N
R2
B(C 6F 5)3
(7 atm)
PMe3
R1
R1
N
PMe3
R2
R1
R1
R1
R1
N
Ni
(C6F3) 3B
O
(C6F3) 3B
N
R2
(7 atm)
Ni
R2
A
1: R1, R2 = H
2: R1 = i-Pr, R2 = H
3: R1, R2 = i-Pr
O
R2
toluene
N
R2
B
n
1: oligomers ,
activity = 1500 kg/molNi·h
2: PE, Mw = 119,000;
activity = 550 kg/molNi·h
3: PE, Mw = 508,000;
activity = 350 kg/molNi·h
toluene
Bazan JACS 2001 (123) 5352.
NDP
A crystal structure of 3 was obtained. The nearly identical
bond distances between Ni and the 2 N atoms (1.91Å,
1.94Å) and the elongated C-O bond suggests that
resonance structure B is a significant contributor to 3's
structure.
M.C. White, Chem 153
Dimerization -309-
Week of November 18, 2002
Nickel promoted olefin dimerizations
Ligand effects...
Cl
Ni
Ni
Cl
+ R 3P
cat.
+
EtAlCl2, chlorobenzene, -45oC
trace
P(Et)3
(i-Pr) 2P(t-Bu)
Product distribution of propylene dimers
formed depends heavily on the phosphine
ligand. Diisopropyl-tert-butylphosphine gives
predominantly 2,3-dimethyl-1-butene and also
showes the highest catalytic activity for
dimerization. In the analogous process with
ethylene, the choice of bulky phosphine effects
whether dimerization or polymerization
occurs.
Very subtle...
Cl
Ni
Ni
Cl
+ R 3P
cat.
EtAlCl2, chlorobenzene, -45oC
n
(t-Bu)3P, polyethylene
(i-Pr) 2P(t-Bu), dimer
Proposed mechanism:
Cl
Ni
Ni
R3P
(i-Pr) 2P(t-Bu) = PR3
NiII
Cl
Cl
EtAlCl2
R3P
δ-
Ni
δ+
EtCl2AlCl
R3P
II
δ-
H
EtCl2AlCl
R3P
II
Ni
δ-
δ+
EtCl2AlCl
NiII
δ+
R3P
R3P
δEtCl2 AlCl
NiII
δ+
δcatalytic cycle
R3P
δEtCl2 AlCl
NiII
δ+
catalyst activation
R3P
H
δ-
EtCl2AlCl
EtCl2AlCl
NiII
δ+
NiII
δ+
H
Wilke ACIEE 1988 (27) 185.
M.C. White, Q. Chen Chem 153
Dimerization -310-
Week of November 18, 2002
Cp2Zr(Cl)/MAO (Zr:Al, 1:1) leads to dimerization
Cp2ZrCl2/MAO
0.5 mol %
Et
Et
(1:1 Zr:Al)
Et
In zirconocene/MAO catalyzed polymerizations, a large excess of MAO is necessary to
effect an efficient process (Al/Zr ratios of 500:1 up to 10,000:1). The Cp2ZrCl2/MAO
(Al/Zr ratio 1:1) system is very selective for the dimerization of terminal olefins over
oligomerization and polymerization. One rationale for this is that an associated Cl promotes
β-hydride elimination over insertion. The reason for this is unclear.
Et
ZrI V
Cl
MAO
ZrIV
Me
ZrI V
δ-
δ+
Cl
Et
δ+
ClAl(MAO)
Et
Me
ZrI V
δ-
?
Et
ZrI V
Et
Et
H
Et
δ-
ClAl(MAO)
Et
Et
H
ZrI V
δ+
ZrIV
δ-
δ+
ClAl(MAO)
Et
Et
ZrIV
δ+
Bergman JACS 1996 (118) 4715.
δ-
ClAl(MAO)
Et
ZrIV
δ+
δ-
ClAl(MAO)
δ-
ClAl(MAO)
ClAl(MAO)
H
δ-
ClAl(MAO)
M.C. White, Chem 153
Cyclodimerization -311-
Week of November 18, 2002
Ni(0) catalyzed 1,3-diene cyclodimerization
Oxidative coupling
concerted
stepwise
oxidative coupling
LnM n
reductive fragmentation (rare)
LnM n+2
LnM n
LnMn+2
LnM n+2
non-bulky
e.g. P(OMe)3
bulky
e.g. P(OPh)3
Ni0(COD) 2, PR 3
basic phosphines
(PPhEt 2)
Proposed mechanism:
Once again, the dimerization product distribution is heavily
dependent on the phosphine ligand used. Basic phosphines
are known to stabilize the 16e- η1,η3-bis-allyl intermediate
which leads to the vinylcyclohexene product. Less basic
phosphites are thought to stabilize the 18e- bis-η3-allyl
forms.
Ni0(COD)2
PR3
R3P Ni0
less basic phosphites
LnNi(0)
NiII
R3P
R3P
η1,η3-bis allyl
R3P NiII
NiII
2 COD
NiII
PR3
H
sterically unfavorable
PR3
favored when
PR3 is bulky
Weimann ACIEE 1980 (19) 569, 570.
Houk JACS 1994 (116) 330.
NiII
NiII
H
PR3NiII
PR3
Note
that
this
mechanism operates
for metals in ligand
enviroments that can
increase
their
oxidation state by 2
units.
M.C. White, Chem 153
[4+4] -312-
Week of November 18, 2002
Wender’s intramolecular cyclodimerization: [4+4]
3 carbon tether:
H
H
EtO2C
EtO2C
Ni(COD)2 (11 mol%)
EtO2C
EtO2C
PPh 3 (33 mol%), tol
EtO2C
EtO2C
o
EtO2C
+
60 C
H
H
70% (19:1)
Ni0Ln
Ln(PPh 3)Ni 0
PPh3
NiII
PPh3
NiII
PPh3
PPh3
2.6% (if P(OTol)3
is used, the vinyl
cyclohexene analog
is the main product
(37% yield)
Ni
Ni0
H
H
EtO2C
oxidative
coupling
H
H
H
H
H
H
4 carbon tether:
CO2Me
MeO2C
An analogous homoallylic substituted substrate
also gave predominantly the trans fused product
but very poor dr (1:2.2). When the allylic ester is
replaced with other bulky functionality, the
diastereoselectivity remains high: CH2OAc (dr
21:1) and CH3 (dr 20:1).
H
Ni(COD)2 (11 mol%)
PPh 3 (33 mol%), tol
60oC
H
Ln(PPh 3)Ni
95:5 (trans:cis)
99:1 (dr)
84%
0
H
etc...
H
PPh3
Ni0
NiII
H
oxidative
coupling
H
PPh3
Wender JACS 1986 (108) 4678.
Wender TL 1987 (28) 2451.
M.C. White, Chem 153
[4+4] -313-
Week of November 18, 2002
Applications of [4+4] in TOS
First application of the [4+4] methodology in the total synthesis of (+)-Asteriscanolide. Wender JACS 1988 (110) 5904.
O
O
O
O
O
H
H
H
O
H
H
H
Ni(COD)2 (11 mol%)
PPh 3 (33 mol%), tol
60oC
67%
H
H
O
(+)-Asteriscanolide
Model studies for the taxane skeleton. Wender TL 1987 (28) 2221.
TBSO
Ni(COD)2 (11 mol%)
TBSO
AcO
PPh 3 (33 mol%), tol
110oC
O
OH
52%
RO
Ni(COD)2 (11 mol%)
PPh 3 (33 mol%), tol
110oC
CO2CH3
H
OH OR OAc
Taxol
H
CO2CH3
92% yield
97% de
O
M.C. White, Chem 153
[4+2] -314-
Week of November 18, 2002
Intramolecular dienyne cycloaddition: [4+2]
3 and 4 carbon tethers used.
2 and 5 carbon tethers do
not cyclize.
R
X
R'
H
Unlike the Ni(0) catalyzed
[4+4], PPh3 ligand results in
slow reactions that are
attended
by
substrate
decomposition and product
aromatization.
H
R
Ni(COD)2 (10 mol%)
P(O-o-biphenyl)3 (30 mol%), THF
rt
X
R
X
R'
R'
R= CH 2OTBS, R'= Me, X= CH2, >99%; (2:1), thermal 160oC
R= CH 2OTBS, R'= TMS, X= CH2, 98% (1.2:1), thermal 140oC
R= CH 2OAc, R'= Me, X = CH2CH2, 85% (1.8:1), thermal 200oC
Proposed mechanism
H
H
H
H
O
The low reactivity of unactivated alkynes
as dienophiles in thermal DA rxns requires
extreme
temperatures
to
effect
cycloadditions. Elevated temperatures
often lead to decomposition, particularly
for substrates with remote functionality.
Alternatively, the Ni(0) promoted
cyclization proceeds at rt with outstanding
yields.
Ni(COD)2 (10 mol%)
P(O-o-biphenyl)3 (30 mol%), THF
rt
rxn proceeds with complete
stereocontrol in C-C bond
formations:
99% yield, (trans: cis, >99:1)
O
Ln(PR 3)Ni 0
Ln(PR 3)Ni 0
O
H
H
NiII
Ni0
Me R P
3
PR3
H
H
O
II
Me
R3P
Wender JACS 1989 (111) 6432.
Ni
O
M.C. White, Chem 153
[4+2] -315-
Week of November 18, 2002
Intramolecular diene-allene cycloaddition: [4+2]
Metal mediated reversal in chemoselectivity...
OTBS
TBSO
Ni(COD)2 (10mol%)
P(O-o-biphenyl)3 (30 mol%)
THF, rt
97%
OTBS
H
R3P
H
Ni0
OTBS
TBSO
·
[Rh(COD)Cl] 2 (5 mol%)
P(O-o-biphenyl)3 (48 mol%)
THF, 45oC
90%
H
H
Cl
R3P
A complete reversal of chemoselectivity
occurs in the metal-mediated [4+2]
diene-allene cycloaddition in switching
from
a
Ni(COD)2
catalyst
to
[Rh(COD)Cl] 2. The known preference for
Ni0 coordination to the less sterically
hindered π-bond of allenes is given as a
rationale for the observed difference in
selectivities.
Rh I H
OTBS
Proposed mechanism:
H
R 3P
R 3P
Cl
Rh I
OTBS
R 3P
OTBS
H
Cl
Rh I
PR3
·
L
OTBS
OTBS
H
R 3P
R 3P
Rh I
Rh III
R3 P
Cl
Cl
TBSO
OTBS
Rh III
Cl
H
H
R 3P
OTBS
H
R3 P
Rh III
Cl
Cl
R3 P
Rh I
H
Wender JACS 1995 (117)1843.
M.C. White, Chem 153
[5+2] -316-
Week of November 18, 2002
Wender’s [5+2] cycloadditions
Efficient route to 7 membered rings via 5+2 cycloadditions of vinylcyclopropanes and...
R
alkenes/alkynes
MeO2C
R
R
O
MeO2C
RhCl(PPh3) 3 (0.1 mol% -0.5 mol%)
R'
H
AgOTf (0.1 mol% - 0.5 mol%)
tol, 110 oC
X
X
83%
R = Me, 88%
TMS, 83%
CO2Me, 74%
t-Bu
allenes
H
MeO2C
R
R
·
H
MeO2C
MeO2C
MeO2C
H
RhCl(PPh 3) 3 (1 mol%)
tol, 110 oC
X
Me
X
H
92%
96%
exclusive formation of the cis-fused product
for the 5,7 ring system. Trans-fused product
observed for the 6,7 ring system.
H
Proposed mechanism:
PPh3
PPh3
RhI
X
-OTf
oxidative
coupling
vinylcyclopropanes are thought to
have diene-like properties because
of significant p orbital character in
the strained σ bond
H
RhIII
X
H
-OTf
PPh3
ring-expansion
PPh 3
PPh3
RhIII
reductive
elimination
X
PPh3
X
H
H
H
H
-OTf
[LnRhI]+ (OTf-)
or...
PPh3
PPh3
Rh III
X
-OTf
exclusive formation of the cis-fused
product is consistent with the
preferential formation of a cis-fused
metallocyclopentane intermediate
Wender JACS 1995 (117) 4720.
Wender JACS 1998 (120) 1940.
Wender JACS 1999 (121) 5348.
for an intermolecular [5+2] w/ alkynes see:
Wender JACS 1998 (120) 10976.
M.C. White, Chem 153
[5+2]-317-
Week of November 18, 2002
Applications of [5+2] in TOS
Me
Me
OH
CHO
(+)-Allocyathin B2
Me
O
Me
[Rh(CO) 2Cl]2
5 mol%
DCE, 80 oC
Me
OH
O
Me
Me
Me OH O
Me
O
RhLn
RhLn
H
H
Me
HO
HO
H
90%
Asymmetric synthesis of tricyclic core of (+)-Allocyathin B2. Wender OL 2001 3:13 2105-2108.
O
H
OBn
(+)-Aphanamol
·
Ln
Rh
[Rh(CO) 2Cl]2
Toluene
100 oC
OBn
RhLn
H
OBn
H
OBn
H
OBn
93%
Asymmetric total synthesis of (+)-Aphanamol I. Wender OL 2000 2:15 2323-2326.
M.C. White, Chem 153
[5+2] -318-
Week of November 18, 2002
Question 1
Propose a mechanism for the following transformation:
O
O
O
CH3
O
H
[Rh(CO) 2Cl]2 (2.5 mol%)
CO (1-2 atm), dioxane, 60 oC
H3O+
+
Et
C(O)CH 3
OH Et
M.C. White, Chem 153
Cycloisomerization -319-
Week of November 18, 2002
Ru mediated cycloisomerization
TBDMSO
R
TBDMSO
CO2CH3
CpRu(CH3CN) 3PF 6
10 mol%
acetone, rt
TBDMSO
CO2CH3
R
R
CpRu(CH3CN) 3PF 6
10 mol%
CO2CH3
acetone, rt
R = Me
R=H
(PF6 -)
Ru II
H3 CNC
TBDMSO
R
CO2CH3
TBDMSO
Ru
H
(IV)
Cp
CNCH3
CNCH3
TBDMSO
CO2CH3
R
R
CO2CH3
Ru(IV)Cp
Cycle A
Ru
(II)
Cycle B
Cp
H
R = Me
R=H
A
A1,3-type strain if R = Me
TBDMSO
CO2CH3
R
Ru(IV)Cp
R=H
TBDMSO
Ru(IV)Cp
R = CH3
H
C
B
To rationalize the observed divergence in reaction course, the authors
suggest that when R = Me the oxidative coupling of A to form B is
disfavored due to steric congestion in the form of A1,3-type strain between
the quaternary center and the ester. Alternatively, allylic C-H activation
leads to the formation of intermediate C, which subsequently cyclizes to a
seven-membered ring
CO2CH3
R
Trost JACS 1999 121 9728-9729.
The allylic C-H activation mechanism is supported by the following
deuterium-labelling experiment
TBDMSO R
TBDMSO R
CO 2CH3
CO 2CH3 CpRu(CH 3 CN)3 PF6
D
D
D
CD3
M.C. White Chem 153
Cycloisomerization -320-
Week of November 18, 2002
Pd mediated cycloisomerization
CO2CH3
CO2CH3
Pd(OAc)2 (5 mol%)
N
N
6 mol%
Ph
Ph
83%
0
Pd 0Ln
Pd Ln
CO2CH3
CO2CH3
CO2CH3
Pd0Ln
Pd IILn
H PdIILn
Trost JACS 1987 (109) 3484.
H
in situ generation of Pd(0) via Wacker type process:
AcOH
CO 2CH3
Pd II(OAc)2Ln
H
CO 2CH3
Pd II(OAc)Ln
Nu
H
CO 2CH3
+
Nu
AcO
PdIILn
Pd 0Ln
Nu
Cy
MeO2C
MeO2C
Pd2(dba)2 (2.5 mol%)
P(o-tol) 3 (5 mol%)
AcOH (5 mol%)
MeO2C
When AcOD was used the
dideuterated product is observed.
The
first
deuterium
is
incorporated via exchange with
acetylene H and the second via the
proposed hydropalladation.
MeO2C
95%
Pd0L n
Cy
AcOH
D
H
II
AcO
H
MeO2C
Pd Ln
MeO2C
MeO2C
Pd OAc
Cy
MeO2C
H
D
MeO2C
Pd(OAc)Ln
MeO2C
Cy
MeO2C
MeO2C
Pd OAc
Cy
Cy
Trost JACS 1994 (116) 4268.
M.C. White, Q. Chen Chem 153
[2+2+2] -321-
Week of November 18, 2002
[2+2+2] cycloaddition of diynes with isocyanates to
give bicyclic pyridones
Ph
+
N
·
Ph
Cp*Ru(COD)Cl
5 mol%
N
O
DCE, reflux, 2h
O
Cp*Ru(COD)Cl
Ph
N
O
Cp*RuCl
RuCp*Cl
RuIICp*Cl
NPh
O
Cp* N Ph
Ru
Itoh. OL 2001 (3) 2117.
Cl
·
O
RuIVCp*Cl
PhNCO
16e-
M.C. White, Chem 153
[4+1] -322-
Week of November 18, 2002
Carbonylative [4+1]
Ru 3(CO) 12 2 mol%
Ph
Nt-Bu
+
CO
(10 atm)
toluene, 180 oC
Nt-Bu
Ph
O
Although α,β-unsaturated imines react readily with early transition metals such as Ti and Zr to form
the corresponding metallacyclopentenes, this is the first example of such a reaction with a late
transition metal complex.
Nt-Bu
Ph
Nt-Bu
Ph
O
O
the authors propose that initial
coordination of a nitrogen to ruthenium
facilitates the oxidative cyclization to
yield the metallacycle intermediate
Ru0(CO)4
CO
for the reaction of imines which contain a
β-hydrogen, olefin isomerization occurs
to give the thermally more stable
α,β-unsaturated γ-lactam
Ru
(CO)3
Nt-Bu
Ph
O
oxidative
cyclization
CO insertion
Ph
Murai JACS 1999 (121) 1758.
Nt-Bu
II
Ru
(CO) 4
Nt-Bu
Ru
(CO)4
M.C. White, M.W. Kanan Chem 15
Cycloisomerization -323-
Week of November 18, 2002
Cycloisomerization/carboxylation of bis-1,3-dienes
H
CO2H
Ni(acac)2 5 mol%
PPh3, 10 mol%
Ni(acac)2 5 mol%
PPh3, 10 mol%
TsN
TsN
CO2, 1 atm
Me2Zn, 4.5 eq.
HF, 0°C
H
H
NiII(acac)2
H
Et2Zn
TsN
H
TsN
CO2, 1 atm
Et2Zn, 4.5 eq.
HF, 0°C
CO2ZnEt
CO2ZnMe
CO2H
H
TsN
H
L nNi0
TsN
H
reductive elimination
TsN
O
H
OZnEt
TsN
reductive
elimination
NiLn
oxidative
coupling
H
H
NiLn
H
NiII
TsN
H
O
OZnMe
TsN
H
Ln
Ni
Me
β-hydride
elimination
H
Mori JACS 2002 (124) 10008.
O
H
OZnEt
TsN
H
this intermediate has no β-hydrogens
H
Ln
Ni
transmetalation
insertion
O
ZnEt2 TsN
Et
O
H
NiL n
O
·
O
M.C. White/Q. Chen Chem 153
Question -324-
Week of November 18, 2002
Question 2
Beginning with 1 propose a synthetic route to 2. Indicate all reagents and show intermediates.
TBDPSO
TBDPSO
OH
1
2
Beginning with 3 propose a synthetic route to 4. Indicate all reagents and show intermediates.
H
TBDPSO
TBDPSO
3
O
4
M.C. White, M.S. Taylor Chem 153
Question -325-
Week of November 18, 2002
Question 3
Provide a mechanism for the following transformation
SiPh3
MeO2C
Ph 3SiD
MeO2C
Pd 2(dba)3 (5 mol%)
THF, 25°C, 2 hours
MeO2C
CH2D
MeO2C
MeO2C
MeO2C
Ph 3Si
DH2C
A
6:1 A:B
B